Several photolabile sirolimus analogs have been synthesized. All ot the compounds showed an antiproliferative effect in a mitogen-induced thymocyte proliferation assay. Compounds 3 and 4 were shown to be equipotent to sirolimus in a murine skin allografi model; they should thus be useful for investigating the in vivo details of the signal transduction pathway(s) modulated by sirolimus. The immunosuppressive effect of analogs 3-5 is corroborated by their ability, as part of an FKBP12 complex, to bind a sirolimus effector protein (SEP).